Cognitive Impairment in Multiple Sclerosis (MS), generally in the form of the so-called SubCortical Dementia, results predominantly by the disruption of communication among Cortical and SubCortical areas, consequent to White Matter damage.

Studies with conventional Magnetic Resonance Imaging (MRI) demonstrated that Cognitive Impairment in MS patients is related to lesion burden, although the strength of this correlation is weak.

This can be partially explained by the poor pathological specificity of conventional MRI techniques and by damage in the Normal-Appearing White Matter (NAWM).

This interpretation is supported by studies using NonConventional MRI techniques, more specific to the heterogeneous substrates of MS pathology.

Such as, the assessment of HypoIntense lesion load on T1-weighted scans, and the measurement of the Magnetization Transfer Ratio (MTR) of whole Brain, MS lesions and NAWM.

Other factors, such as the site of MS lesions and the presence of active inflammation, also seem to play an important role.

Neuronal damage seems to be a major source of disability in Multiple Sclerosis (MS) patients and at present Magnetic Resonance Imaging (MRI) is a sensitive method to evaluate lesion and disease activity.

We studied the potential correlation between changes in MS patients' disability after relapse, the degree of T1 lesion HypoIntensity on MRI in vivo and Neuronal Apoptosis induced by CerebroSpinal Fluid (CSF) on Neuron cultures.

In this study, we included 24 MS patients with Relapsing disease. Clinical recovery from relapse was measured by the Expanded Disability Status Scale (EDSS).

T1-weighted MRI studies were done according to established standards and Neuronal Apoptosis was induced by treatment of Neuronal cultures with CSF from patients while relapsing.

Whereas, all CSF that did not induced such effects corresponded to patients without T1 lesions.

The recovery from an acute MS relapse is significantly worse in patients with HypoIntense T1 lesions in MRI and in those whose CSF damaged Neurons on cultures in vitro, phenomena that closely correlated each other.

#4

The Effect Of IFN-ß-1b On The Evolution Of Enhancing Lesions In Secondary/Progressive MS

Background
After the resolution of contrast enhancement, the majority of new MS lesions become IsoIntense with surrounding White Matter on T1-weighted MRI.

Less commonly, a HypoIntense T1 lesion develops, representing the development of more severe focal tissue damage.

Interferon-beta (IFN-ß) reduces both the number of new enhancing lesions and the duration of contrast enhancement.

Objective
To determine if IFN-ß affects the degree of tissue damage within new lesions and if its effects are related to lesion size.

Methods
One hundred twenty-five patients with Secondary/Progressive MS from seven European sites were randomized to receive either IFN-ß-1b or placebo.

Monthly, contrast-enhanced T1-weighted MR images were acquired at baseline, at months 1 to 6, and at months 19 to 24.

The size of all new enhancing lesions developing between months 1 and 6 was recorded and their appearance at follow-up documented.

Results
In the first 6 months, fewer new enhancing lesions occurred in the IFN-ß-1b arm. This difference was greater for small (70% decrease) than for large (46% decrease) lesions.

HypoIntense T1 lesions were more likely to form from large (25%) than from small (9%) enhancing lesions in both treatment arms.

Patients taking IFN-ß-1b developed fewer HypoIntense T1 lesions; however, the proportion of enhancing lesions developing into HypoIntenseT1 lesions was similar in both arms.

ConclusionIFN-ß-1b reduced the number of new enhancing lesions, with a greater effect on small lesions. However, when a new enhancing lesion did become established, treatment with IFN-ß-1b did not alter its subsequent course.

#5

In Vivo Assessment Of The Brain And Cervical Cord Pathology Of Primary/Progressive Multiple Sclerosis

On the contrary, the degree of Cord Atrophy and diffuse tissue damage in the Brain and Cervical Cord have been found to be associated with clinical disability.

Against this background, this study aimed at providing an in vivo indirect assessment of Brain and Cervical Cord pathology in a large cohort of PP Multiple Sclerosis patients, using conventional MRI and Magnetization Transfer Imaging (MTI).

The relation between Atrophy during the original trial and disability status at follow-up was determined.

Correlations were also determined between lesion measurements from the original trial and the Brain Parenchymal Fraction at follow-up.

Results
Brain Atrophy was correlated with subsequent disability status. Atrophy rate during the original trial was the most significant MRI predictor of disability status at follow-up.

Brain Atrophy at follow-up was related to lesion volumes measured during the original trial.

Conclusions
The relation between Atrophy progression and subsequent Neurologic Disability Status suggests that Atrophy progression during RRMS is clinically relevant.

Therefore, Atrophy progression may be a useful marker for disease progression in clinical trials.

The relation between lesions and subsequent Atrophy indicates that Brain Atrophy may be related to focal tissue damage at earlier points in time, but important predisposing or other factors contributing to Atrophy remain undefined.

The ADC and Anisotropy of normal tissue from standard regions were compared with HyperIntensities from these regions. The Students' t test compared individual regions and averaged White Matter results.

Results
HyperIntensities showed higher ADC and lower Anisotropy than normal regions. Gray Matter exhibited similar trends. There was no significant difference in Diffusion characteristics of HyperIntensities between subjects and control subjects.

Conclusions
HyperIntensities damage the structure of Brain Tissue, and do so comparably in Depressed subjects and control subjects.

Purpose
To determine the Fractional Brain Tissue Volume changes in the Gray Matter and White Matter of patients with Relapsing/Remitting Multiple Sclerosis (MS) and to correlate these measurements with clinical disability and total lesion load.

This study investigates water Diffusion changes in Wallerian Degeneration.

We measured indices derived from the Diffusion Tensor (DT) and T2-weighted signal intensities in the Descending Motor Pathways of patients with small chronic Lacunar Infarcts of the Posterior Limb of the Internal Capsule on one side.

We compared these measurements in the healthy and lesioned sides at different levels in the BrainStem caudal to the primary lesion.

We found that secondary White Matter degeneration is revealed by a large reduction in Diffusion Anisotropy only in regions where Fibers are arranged in isolated bundles of parallel Fibers, such as in the Cerebral Peduncle.

In regions where the Degenerated Pathway crosses other Tracts, such as in the rostral Pons, paradoxically there is almost no change in Diffusion Anisotropy, but a significant change in the measured orientation of Fibers.

The trace of the Diffusion Tensor is moderately increased in all affected regions. This allows one to differentiate secondary and primary Fiber loss where the increase in trace is considerably higher.

We show that DT-MRI is more sensitive than T2-weighted MRI in detecting Wallerian Degeneration. Significant Diffusion abnormalities are observed over the entire trajectory of the affected Pathway in each patient.

This finding suggests that mapping Degenerated Pathways noninvasively with DT-MRI is feasible. However, the interpretation of water Diffusion data is complex and requires a priori information about Anatomy and architecture of the Pathway under investigation.

In particular, our study shows that in regions where Fibers cross, existing DT-MRI-based Fiber tractography algorithms may lead to erroneous conclusion about Brain connectivity.

The main outcome measures were the MRI parameters and disability on Kurtzkes' Expanded Disability Status Scale. There was a significant correlation between the change (increase) in T1 lesion volume and progressive Cerebral Atrophy

Whereas, no correlation between the T2 lesion volume and Atrophy was seen over the same follow-up period.

The change in T1 lesion volume correlated more strongly than did T2 lesion volume change with the change in disability.

We conclude that HypoIntense abnormalities detected in T1-weighted Brain scans and Cerebral Atrophy may be directly linked.

Although one should bear in mind some potential for reversibility due to inflammatory, Edematous lesions, these MR measures are a useful marker of progressive tissue damage and clinical progression in established MS.

Magnetic Resonance Imaging (MRI) plays an ever-expanding role in the evaluation of Multiple Sclerosis (MS).

This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected Clinically Isolated Syndromes.

The utility of MRI stems from its sensitivity to longitudinal changes including those in overt lesions and, with advanced MRI techniques, in areas affected by diffuse occult disease (the so-called Normal-Appearing Brain Tissue).

However, all current MRI methodology suffers from limited specificity for the underlying histopathology.

Conventional MRI techniques, including lesion detection and measurement of atrophy from T1- or T2-weighted images, have been the mainstay for monitoring disease activity in clinical trials.

In which the use of Gadolinium with T1-weighted images adds additional sensitivity and specificity for areas of acute inflammation.

And, may provide methods to monitor therapies more sensitively in the future.

However, these advanced methods are limited by their cost, availability, complexity, and lack of validation. In this article, we review the role of conventional and advanced imaging techniques with an emphasis on NeuroTherapeutics.